Peptide-drug Conjugate Information
General Information of This Peptide-drug Conjugate (PDC)
| PDC ID |
PDC_00358
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| PDC Name |
GLP-1-MK-801
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| PDC Status |
Preclinical
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| Indication |
In total 1 Indication(s)
Obesity
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| Structure |
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| Peptide Name |
GLP-1 analogue
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Peptide Info | ||||
| Receptor Name |
Glutamate receptor ionotropic, NMDA 1 (GRIN1)
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Receptor Info | ||||
| Drug Name |
Dizocilpine
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Drug Info | ||||
| Therapeutic Target |
Glutamate receptor ionotropic, NMDA 3A (GRIN3A)
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Target Info | ||||
| Linker Name |
Disulfide bond
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Linker Info | ||||
| Formula |
C203H291N47O63S2
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| #Ro5 Violations (Lipinski): 5 | Molecular Weight | 4461.961 | ||||
| Lipid-water partition coefficient (xlogp) | -15.292 | |||||
| Hydrogen Bond Donor Count (hbonddonor) | 56 | |||||
| Hydrogen Bond Acceptor Count (hbondacc) | 63 | |||||
| Rotatable Bond Count (rotbonds) | 144 | |||||
Full List of Activity Data of This Peptide-drug Conjugate
Obtained from the Model Organism Data
| Experiment 1 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Obesity | ||||
| Efficacy Data | Fat mass reduction rate |
45%
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| Administration Time | Once a day for 14 days | ||||
| Administration Dosage | 100 nmol kg-1 | ||||
| Evaluation Method | GLP-1-MK-801 produced a vehicle-corrected reduction in body fat mass of 45%, accompanied by an 8% loss in lean mass. | ||||
| MOA of PDC |
Treatment with GLP-1-inactive MK-801 produced no additional weight loss efficacy relative to GLP-1 monotherapy (Fig. 2g-i), indicating that the pronounced weight loss induced by GLP-1-MK-801 is driven by concerted and site-directed pharmacological GLP-1 receptor agonism and NMDA receptor antagonism.
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| In Vivo Model | DIO mice | ||||
| Half life period | 1.9 h | ||||
| Experiment 2 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Obesity | ||||
| Efficacy Data | Lean mass rate |
8%
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| Administration Time | Once a day for 14 days | ||||
| Administration Dosage | 100 nmol kg-1 | ||||
| Evaluation Method | GLP-1-MK-801 produced a vehicle-corrected reduction in body fat mass of 45%, accompanied by an 8% loss in lean mass. | ||||
| MOA of PDC |
Treatment with GLP-1-inactive MK-801 produced no additional weight loss efficacy relative to GLP-1 monotherapy (Fig. 2g-i), indicating that the pronounced weight loss induced by GLP-1-MK-801 is driven by concerted and site-directed pharmacological GLP-1 receptor agonism and NMDA receptor antagonism.
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| In Vivo Model | DIO mice | ||||
| Half life period | 1.9 h | ||||
| Experiment 3 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Obesity | ||||
| Efficacy Data | Vehicle-corrected weight loss rate |
9.50%
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| Administration Time | 1 dose | ||||
| Administration Dosage | 0.22 nmol | ||||
| Evaluation Method | This study revealed a superior vehicle-corrected weight loss of 9.5% in response to the GLP-1-MK-801 infusion relative to a weight loss of 4.5% after semaglutide infusion (Fig. 4b). | ||||
| MOA of PDC |
Treatment with GLP-1-inactive MK-801 produced no additional weight loss efficacy relative to GLP-1 monotherapy (Fig. 2g-i), indicating that the pronounced weight loss induced by GLP-1-MK-801 is driven by concerted and site-directed pharmacological GLP-1 receptor agonism and NMDA receptor antagonism.
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| In Vivo Model | High-fat high-sucrose-fed mice | ||||
| Half life period | 1.9 h | ||||
| Experiment 4 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Obesity | ||||
| Efficacy Data | Vehicle-corrected weight loss rate |
15.20%
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| Administration Time | Once a day for 9 days | ||||
| Administration Dosage | 100 nmol kg-1 | ||||
| Evaluation Method | We observed a pronounced vehicle-corrected weight loss of 15.2% in the group treated with GLP-1-MK-801 compared with 3.5% in the group treated with the parent GLP-1 analogue after 9days of treatment, underscoring that the weight-lowering efficacy of the conjugate is intact in the absence of functional MC4R signalling (Fig. 3l,m). | ||||
| MOA of PDC |
Treatment with GLP-1-inactive MK-801 produced no additional weight loss efficacy relative to GLP-1 monotherapy (Fig. 2g-i), indicating that the pronounced weight loss induced by GLP-1-MK-801 is driven by concerted and site-directed pharmacological GLP-1 receptor agonism and NMDA receptor antagonism.
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| In Vivo Model | Mc4r-KO mice | ||||
| Half life period | 1.9 h | ||||
| Experiment 5 Reporting the Activity Data of This PDC | [1] | ||||
| Indication | Obesity | ||||
| Efficacy Data | Vehicle-corrected weight loss rate |
23.20%
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| Administration Time | Once a day for 14 days | ||||
| Administration Dosage | 100 nmol kg-1 | ||||
| Evaluation Method | Over a 14-day treatment period, GLP-1-MK-801 synergistically lowered body weight compared with the dose-matched monotherapies and produced a vehicle-corrected weight loss of 23.2%. | ||||
| MOA of PDC |
Treatment with GLP-1-inactive MK-801 produced no additional weight loss efficacy relative to GLP-1 monotherapy (Fig. 2g-i), indicating that the pronounced weight loss induced by GLP-1-MK-801 is driven by concerted and site-directed pharmacological GLP-1 receptor agonism and NMDA receptor antagonism.
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| In Vivo Model | DIO mice | ||||
| Half life period | 1.9 h | ||||
References